Founded and organized by John Bryan Bowman, the University of Kentucky was chartered in February of 1865 by the Kentucky Legislature, as the Agricultural and Mechanical   (A&M) College of Kentucky, a department established, pursuant to the terms of the Morrill Land-Grant Act of 1862, for the purpose of college-level training in agriculture and       engineering within Kentucky University, a private, sectarian institution organized at the same time.

James K. Patterson became the presiding officer of the Kentucky University's A&M College in 1869. Ensuing denominational and theological controversies, as well as financial difficulties, prompted the state legislature to formally separate the college from the Kentucky University in 1878. By 1880, the A&M College began development as an independent institution of higher education, under the leadership of Patterson, on the site of a municipal park and fairgrounds donated by the city of Lexington. During this period the institution was often referred to as State College.

Even with the university weakened by financial hardship, one of Patterson's first administrative efforts was building a campus. He would go on to oversee the construction of the college's first three buildings on its new Lexington Fairgrounds site. The original three buildings were President Patterson's house, home to the office of the Dean of Arts and Sciences College; the original White Hall, a dormitory; and UK's Administration Building. The buildings were finished in 1882, ultimately at Patterson's own expense, after he risked his savings as collateral for the construction. The construction of more buildings would follow during Patterson's term, including Pence Hall and Alumni Hall, now Barker Hall. In addition, Patterson secured a library built by Andrew Carnegie that was located near where today's White Hall Classroom Building sits. President Patterson would relinquish his office in 1910.

The board chose as the next president a judge, Henry Stites Barker. A period of steady and substantial growth, Barker's administration established the Graduate SchoolDepartment of Journalism and YMCA on campus. During his tenure the institution was given its final name, University of Kentucky, in 1916 as part of a state statute. The Reserve Officers Training Corps (ROTC), also known as the Student Army Training Corps, was set up in 1917 to provide instruction for military personnel participating in World War I. Barker's administration also saw the addition of the first printing press on campus, procured at the president's own expense. Barker's administration saw the addition of the first printing press on campus procured at the president's own expense. Meanwhile, student activities expanded during this time. The student newspaper — The Idea — and its successor, the Kentucky Kernel (introduced in fall of 1915), were published weekly and attracted a broad and active readership, and Student Government had its origins in the Student Self-Government Organization founded in 1912. Moreover, Barker, a proponent of physical training, encouraged student participation in athletics, and basketball and football in particular flourished during his tenure.

In 1917, Frank L. McVey was named UK's third president. While much many of his early years in the office were occupied with keeping the university afloat through World War I, McVey would go on to be credited with ushering the institution into the modern era. Under his leadership, UK emerged intact from a national economic depression due to prudent fiscal policies, and with the war over, began to grow and enrollment jumped. With the help of new additional tax support from the state, President McVey began an ambitious campus building program that would lead to the construction of such buildings as Alumni Gym, Memorial Hall, Margaret I. King Library, Boyd and Jewell dormitories, and the Education Building (later named Taylor Education Building). In addition, Maxwell Place was purchased in 1917 to replace the original president's home, and McVey was the first UK president to reside there until his retirement in 1940.

Herman Lee Donovan served as president of UK for 15 years, from 1941 until 1956. An educator by training and profession, he guided the university through the crises of racial integration after a federal district court in the Lyman Johnson case required the university to admit blacks to graduate and professional programs. Donovan's administration also led the university through World War II and its aftermath. Like his predecessors, he fought vigorously to extend faculty rights and to improve salaries for his professors. Donovan also sought to enhance the status and image of the university by recruiting exceptional young talent and increasing the number of extension services offered in the Central Kentucky region.

When President Frank G. Dickey took the helm in 1957, America's colleges and universities were facing a "crisis" as studies showed the numbers of men and women enrolled in higher education would double from 3 million to 6 million by 1970. Acknowledging UK was "in no shape to cope with such a vast multiplication of students," Dickey unveiled his ideas for expansion of the campus to serve the 12,000 to 15,000 students UK expected enrolled by 1965. To answer the needs of an expanding campus Dickey's administration acquired an extensive addition of land and saw the completion of Holmes, Blazer and Haggin halls; Shawneetown and Cooperstown; the Chemistry-Physics Building; the original Pharmacy Building; and the start of the Agricultural Science building. Dickey also began opening off-campus extension centers that would lead to the creation of UK's community college system years later.

However, the highlight of Dickey's administration was the creation and establishment of a medical center on campus. In 1954, in response to a feasibility study begun at the end of President Donovan's term, UK announced plans for a center that would include colleges of medicine, dentistry and nursing; a hospital; student health service; and a medical library. In 1956, with Governor A.B. Chandler's public support and after a personal appeal by President Dickey to the Kentucky General Assembly, an initial appropriation of $5 million was approved for UK's proposal. The first medical students were admitted in the fall of 1960, just three years before Dickey would resign to take a job as director of the Southern Association of Colleges and Schools.

John W. Oswald, who became president of UK in 1964, was also cognizant of the continued growth in enrollment. He would lay out a plan for how the university would bridge the gap between its first and second centuries including changes to infrastructure that would hopefully accommodate the growing student body.

Oswald's presidency included an expansion of UK's physical plant and the completion of the Agricultural Science building; College of Engineering's Anderson Hall; a Commerce building, now home to the Gatton College of Business and Economics; College of Education's Dickey Hall; and a new College of Law. In addition, a dormitory complex for male and female students that would come to be known as the Kirwan-Blanding Complex was finished. Oswald also began construction of a high-rise office tower and an Arts and Sciences classroom building that would later become Patterson Office Tower and White Hall Classroom Building. Oswald, UK's sixth president, resigned the presidency in 1968. He would go on to serve as president of Pennsylvania State University from 1970 to 1983 before retiring.

When Oswald resigned in 1968, interim president Albert Dennis Kirwan, alumnus and a professor of history and former graduate school dean, attempted to bring calm to the campus. While maintaining balance on campus, Kirwan helped the search committee select his successor. For his service, he was retroactively given the title of seventh president of UK by the Board of Trustees in fall of 1969.

When Otis A. Singletary took over the presidency in 1969, the nation was experiencing a tumultuous time in U.S. history as the public became disenchanted with the country's participation in the Vietnam War. Due to the restlessness on campuses across the nation, very few believed Singletary's term would last very long, including the new president who wasn't sure himself how long he would continue an academic life. Instead, it would mark the beginning of 18 years of service that would be characterized as a period of sustained physical and institutional growth.

A large physical expansion program was carried out under the Singletary administration to keep up with the growing student enrollment. Academic and athletic facilities alike boomed during President Singletary's time in office. UK would see the addition of the Seaton Center, Shively Sports Center with its Nutter Training Facility, Commonwealth Stadium, the south building of the Agricultural Sciences Center, Tobacco and Health Research Institute, Hilary J. Boone Center, Warren Wright Medical Plaza complex, the Medical Annex, College of Nursing and Morgan Biological Sciences buildings, the Student Center Addition, the Singletary Center for the Arts, and the north addition to the Margaret I. King Library (now the Lucille C. Little Fine Arts Library and Learning Center). Singletary retired in June of 1987, having served the institution longer than any of UK's previous presidents except Patterson and McVey.

In July of 1987, David P. Roselle assumed the presidency of UK. His announced goal was to achieve national recognition for the university with respect to the quality of its graduates and its scholarship and research. Consistent with his belief that the then new computation and communications technology was of paramount importance to academic institutions, he helped design and implement a strategy for providing wider access to information technology on the UK campus. A new position — that of Vice President for Information Systems — was created to oversee the Computing Center, all data administration issues, communications, print shops and the library. In fact, UK was one of a small number of universities in the country at the time to have acquired a supercomputer.

Much of Roselle's time and attention at Kentucky was devoted to responding to official National Collegiate Athletics Association allegations of misconduct on the part of the basketball program, in the area of recruiting, and he was widely praised for his handling of the scandal, which erupted in 1988. Amid concern regarding the state legislature's support for the university and in the aftermath of the athletics scandal, in December of 1989 Roselle accepted an offer to become President of the University of Delaware.

Charles T. Wethington Jr. was named UK's 10th president in 1990. The third educationalist to serve UK as president, his 11-year tenure was marked by physical growth and an impressive enhancement in academic stature on the part of the institution. Wethington would oversee the beginning or completion of 41 building projects during his term including the Center for Robotics and Manufacturing Systems, the Agricultural Engineering Building, Bruce Poundstone Agricultural Regulatory Services Building, the Civil Engineering and Transportation Facility, ASTeCC, the Health Sciences Building, Kentucky Clinic North, Stuckert Career Center, Hardymon Building, and the Gill Heart Institute and Surgery Center. The highlight of Wethington's term to many is the campaign for and construction of a new state-of-the-art library on the university campus. William T. Young Library, the new central library in the university library system, opened April 3, 1998. The facility, a favorite among many UK students, houses the general undergraduate collection and social science, humanities, business, biology and agricultural materials. Wethington retired from the presidency in 2001.

Most recently, President Lee T. Todd Jr. spearheaded an effort to revitalize health care in Kentucky. As part of that effort, Todd unveiled plans in 2006 for the Commonwealth's Medical Campus of the Future, a multi-phased project aimed at providing Kentuckians with cutting-edge, 21st century health care. As part of this renovation of the university's medical campus, UK built a new College of Pharmacy and University Health Service facility and started construction of a new, 1 million square foot UK Albert B. Chandler Hospital. Pavilion A of the hospital opened in 2011. In addition, Todd's term saw the opening of four new residence halls, Baldwin, Ingels, Smith and New North (now named Roselle Hall), and the construction of the first Leadership in Energy and Environmental Design (LEED) rated academic facility, the Davis Marksbury Building. Todd's administration also saw the creation of UK's first vice presidency for institutional diversity and the reopening of the Main (Administration) Building, which was severely damaged by fire in May 2001. The Main Building was officially reopened in October 2004. In addition to all his work on campus, Todd's administration saw the implementation of programs aimed at boosting Kentucky's economy. President Todd retired in the summer of 2011.